Dosage Forms

Pharmacologic Category

Aminoquinoline (Antimalarial)

Antimalarial Agent

Pharmacology

Primaquine is an antiprotozoal agent active against exoerythrocytic stages of Plasmodium ovale and P. vivax, also active against the primary exoerythrocytic stages of P. falciparum and gametocytes of Plasmodia; disrupts mitochondria and binds to DNA

Contraindications

Severe G6PD deficiency; pregnancy; use in acutely ill patients who have a tendency to develop granulocytopenia (eg, rheumatoid arthritis, systemic lupus erythematosus); concurrent use with other medications causing hemolytic anemia or myeloid bone marrow suppression; concurrent use with or recent use of quinacrine

Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to primaquine or any component of the formulation

Documentation of allergenic cross-reactivity for aminoquinolines is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Chemoprophylaxis (off-label use): 0.5 mg/kg once daily (maximum dose: 30 mg/day); start 1 to 2 days prior to travel and continue for 7 days after departure from malaria-endemic area (CDC Yellow Book 2014)

Dosing: Renal Impairment

There are no dosage adjustments provided in the manufacturer’s labeling.

Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturer’s labeling.

Extemporaneously Prepared

A 6 mg base/5 mL oral suspension may be made using tablets. Crush ten 15 mg base tablets and reduce to a fine powder. In small amounts, add a total of 10 mL Carboxymethylcellulose 1.5% and mix to a uniform paste; mix while adding Simple Syrup, NF to almost 125 mL; transfer to a calibrated bottle, rinse mortar with vehicle, and add quantity of vehicle sufficient to make 125 mL. Label "shake well" and "refrigerate". Stable 7 days.

Administration

Administer with meals to decrease adverse GI effects. If patient vomits within 30 minutes of taking a dose, then they should repeat the dose (CDC 2013).

Storage

Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from light.

Drug Interactions

Abiraterone Acetate: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Management: Avoid concurrent use of abiraterone with CYP2D6 substrates that have a narrow therapeutic index whenever possible. When concurrent use is not avoidable, monitor patients closely for signs/symptoms of toxicity. Consider therapy modification

Artemether: May enhance the adverse/toxic effect of Antimalarial Agents. Management: Artemether/Lumefantrine (combination product) should not be used with other antimalarials unless there is no other treatment option. Avoid combination

CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

Dapsone (Systemic): May enhance the adverse/toxic effect of Antimalarial Agents. Specifically, concomitant use of dapsone with antimalarial agents may increase the risk for hemolytic reactions. Antimalarial Agents may enhance the adverse/toxic effect of Dapsone (Systemic). Specifically, concomitant use of antimalarial agents with dapsone may increase the risk of hemolytic reactions. Management: Closely monitor patients for signs/symptoms of hemolytic reactions with concomitant use of dapsone and antimalarial agents, particularly in patients deficient in glucose-6-phosphate dehydrogenase (G6PD), methemoglobin reductase, or with hemoglobin M. Consider therapy modification

Dapsone (Topical): Antimalarial Agents may enhance the adverse/toxic effect of Dapsone (Topical). Specifically, the risk of hemolytic reactions may be increased. Management: Closely monitor for signs/symptoms of hemolytic reactions with concomitant use of topical dapsone and antimalarial agents. Patients with glucose-6-phosphate dehydrogenase deficiency may be at particularly high risk for adverse hematologic effects. Consider therapy modification

Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Consider therapy modification

Lumefantrine: Antimalarial Agents may enhance the adverse/toxic effect of Lumefantrine. Management: Artemether/Lumefantrine (combination product) should not be used with other antimalarials unless there is no other treatment option. Avoid combination

Mefloquine: Aminoquinolines (Antimalarial) may enhance the adverse/toxic effect of Mefloquine. Specifically, the risk for QTc-prolongation and the risk for convulsions may be increased. Mefloquine may increase the serum concentration of Aminoquinolines (Antimalarial). Management: Avoid concurrent use, and delay administration of mefloquine until at least 12 hours after the last dose of an aminoquinoline antimalarial when possible. Avoid combination

Mitotane: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Consider therapy modification

Nitric Oxide: May enhance the adverse/toxic effect of Methemoglobinemia Associated Agents. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Management: Monitor patients for signs of methemoglobinemia (e.g., hypoxia, cyanosis) when nitric oxide is used in combination with other agents associated with development of methemoglobinemia. Avoid lidocaine/prilocaine. Monitor therapy

Pitolisant: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Combined use of pitolisant with a CYP3A4 substrate that has a narrow therapeutic index should be avoided. Other CYP3A4 substrates should be monitored more closely when used with pitolisant. Consider therapy modification

Prilocaine: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Prilocaine. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Management: Monitor patients for signs of methemoglobinemia (e.g., hypoxia, cyanosis) when prilocaine is used in combination with other agents associated with development of methemoglobinemia. Avoid lidocaine/prilocaine in infants receiving such agents. Monitor therapy

QTc-Prolonging Agents (Moderate Risk): May enhance the QTc-prolonging effect of other QTc-Prolonging Agents (Moderate Risk). Management: Avoid such combinations when possible. Use should be accompanied by close monitoring for evidence of QT prolongation or other alterations of cardiac rhythm. Consider therapy modification

• Hematologic effects: Anemia, methemoglobinemia, and leukopenia have been associated with primaquine use; monitor during treatment; do not exceed recommended dosage and duration. Closely monitor patients who have a family or personal history of hemolytic anemia or who have had a prior hematologic adverse reaction attributed to primaquine. Immediately discontinue if marked darkening of the urine or sudden decrease in hemoglobin concentration or leukocyte count occurs.

• Hemolytic anemia: Promptly discontinue with signs of hemolytic anemia (darkening of urine, marked fall in hemoglobin or erythrocyte count). Moderate to severe hemolytic reactions may occur in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency and personal or familial history of favism. Geographic regions with a high prevalence of G6PD deficiency (eg, Africa, southern Europe, Mediterranean region, Middle East, southeast Asia, Oceania) are associated with a higher incidence of hemolytic anemia.

Disease-related concerns:

• G6PD deficiency: Screen for G6PD deficiency prior to therapy initiation. Use is contraindicated in patients with severe G6PD deficiency. Assess benefits/risks of treatment when considering use in patients with mild to moderate G6PD deficiency or those patients whose G6PD status is unknown and testing is not available. Also assess risk factors for G6PD deficiency or favism in patients with unknown G6PD status. If a decision is made to administer primaquine to a patient with mild to moderate G6PD deficiency or unknown G6PD status (when testing is not available), perform baseline hematocrit and hemoglobin testing and closely monitor hematological parameters (eg, at day 3 and 8). Immediately discontinue treatment if signs of hemolytic anemia occur.

• NADH methemoglobin reductase deficiency: Use with caution in patients with a personal or family history of NADH methemoglobin reductase deficiency; methemoglobinemia may occur.

Pregnancy Considerations

Primaquine is contraindicated in pregnant women.

Sexually active females should have a pregnancy test prior to treatment with primaquine. Females of reproductive potential should use effective contraception during therapy and until the next menses following discontinuation of treatment. Males with female partners of reproductive potential should use condoms during therapy and for 3 months after treatment is discontinued.

Malaria infection in pregnant women may be more severe than in nonpregnant women and has a high risk of maternal and perinatal morbidity and mortality. Therefore, pregnant women and women who are likely to become pregnant are advised to avoid travel to malaria-risk areas. When treatment is needed, other agents are preferred (CDC Yellow Book 2016). Consult current CDC guidelines for the treatment of malaria during pregnancy.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.